Discovery of novel dihydronaphthalene-imidazole ligands as potential inhibitors of Staphylococcus aureus multidrug resistant NorA efflux pump: A combination of experimental and in silico molecular docking studies.

Overexpression of the efflux pump is a predominant mechanism by which bacteria show antimicrobial resistance (AMR) and leads to the global emergence of multidrug resistance (MDR). In this work, the inhibitory potential of library of dihydronapthyl scaffold-based imidazole derivatives having structural resemblances with some known efflux pump inhibitors (EPI) were designed, synthesized and evaluated against efflux pump inhibitor against overexpressing bacterial strains to study the synergistic effect of compounds and antibiotics. Out of 15 compounds, four compounds (Dz-1, Dz-3, Dz-7, and Dz-8) were found to be highly active. DZ-3 modulated the MIC of ciprofloxacin, erythromycin, and tetracycline by 128-fold each against 1199B, XU212 and RN4220 strains of S. aureus respectively. DZ-3 also potentiated tetracycline by 64-fold in E. coli AG100 strain. DZ-7 modulated the MIC of both tetracycline and erythromycin 128-fold each in S. aureus XU212 and S. aureus RN4220 strains. DZ-1 and DZ-8 showed the moderate reduction in MIC of tetracycline in E. coli AG100 only by 16-fold and 8-fold, respectively. DZ-3 was found to be the potential inhibitor of NorA as determined by ethidium bromide efflux inhibition and accumulation studies employing NorA overexpressing strain SA-1199B. DZ-3 displayed EPI activity at non-cytotoxic concentration to human cells and did not possess any antibacterial activity. Furthermore, molecular docking studies of DZ-3 was carried out in order to understand the possible binding sites of DZ-3 with the active site of the protein. These studies indicate that dihydronaphthalene scaffolds could serve as valuable cores for the development of promising EPIs.

Design, synthesis, and biological evaluation of 3-benzenesulfonamide-linked 3-hydrazinoisatin derivatives as carbonic anhydrase inhibitors.

A new series of isatin-linked benzenesulfonamide derivatives (9a-w) were synthesized using the tail approach and assayed for their inhibitory potency against four different human carbonic anhydrase (hCA) isoforms, hCA I, II, IX, and XII. Most of these synthesized compounds exhibited interesting inhibition potency against isoforms hCA I, IX, and XII in the nanomolar range and by taking the standard drug acetazolamide. The most potent compounds in the case of hCA I were 9c (435.8 nM) and 9s (956.4 nM), for hCA IX, 9a (60.5 nM), 9d (95.6 nM), 9g (92.1 nM), and 9k (75.4 nM), and for hCA XII, 9p (84.5 nM). However, these compounds showed more selectivity toward hCA IX over hCA I, II, and XII. Thus, these compounds can be further developed as potential lead molecules for the development of isoform-selective hCA IX inhibitors with further structural modifications.

Supported nanostructured photocatalysts: the role of support-photocatalyst interactions.

Heterogeneous photocatalysis employing semiconductor oxide photocatalysts is a sustainable and promising method for environmental remediation and clean energy generation. In this context, nanostructured photocatalysts, with at least one dimension in the 1‒100 nm size regime, have attracted ever-growing attention due to their unique and often enhanced size-dependent physicochemical properties. While their reduced size ensures enhanced photocatalytic performance, the same makes it difficult and time/energy-demanding to remove/recover such nanostructured photocatalysts from aqueous media. This fundamental limitation has paved the way towards developing supported nanophotocatalysts where the active photocatalytic nanostructures are coated on the surface of polymeric or inorganic support materials, often in a core@shell conformation. This arrangement solves the problem of photocatalysts' recovery for effective reuse or recycling and leads to improved and desired target properties due to specific photocatalyst-support interactions. While the enhanced physicochemical properties of supported photocatalysts have been widely studied in many target applications, the role of support-photocatalysts interactions in improving these properties remains unexplored. This review article provides an updated viewpoint on the photocatalyst-support interactions and the resulting unique physiochemical properties important for diverse photochemical applications and the design of practical devices. While exploring the properties of supported nanostructured metal oxide/sulfides photocatalysts such as TiO2 and MoS2, we also briefly discuss the common strategies employed to coat the active nanomaterials on the surface of different supports (organic/polymeric, inorganic, active, inert, and magnetic).

Autoimmune epilepsy, retrospective case series of clinical features, management, and outcomes.

OBJECTIVES: To evaluate the clinical and electrographic features of patients with autoimmune epilepsy and assess the influence of early diagnosis and treatment on reducing seizure frequency. METHODS: A retrospective observational case series was conducted utilizing medical records from King Abdullah Medical Hospital between 2017 and 2022. Cases of newly diagnosed seizures were chosen based on laboratory-proven autoimmunity. RESULTS: Five female inpatients were identified, primarily presenting with seizures suggestive of an autoimmune origin. Autoimmune antibodies were detected in all patients as follows: GAD (3), NMDA-R (2). One patient exhibited unilateral temporal lobe onset while three displayed bilateral onset. One patient had an associated malignancy. Rituximab was administered as an immunomodulatory therapy to four patients, resulting in successful seizure reduction post-immunotherapy initiation. CONCLUSION: Autoimmune epilepsy is recognized as a distinct condition. The clinical presentation can be complex and antibody testing may warrant repetition if initial results are negative or if specific antibodies are not detected. Early initiation of immunosuppression, coupled with prompt treatment escalation when required, is vital for achieving optimal patient outcomes.

Eco-friendly dual-edged management of fly ash and its antagonistic interplay with Meloidogyne incognita on beetroot (Beta vulgaris L.).

Fly ash (FA) management is a key concern of ecologists around the world, so its potential as a nutritional supplement for agro-ecosystems needs to be explored. Therefore, alternate techniques that are eco-friendly to manage this emerging dual-edged waste are preferable in this field. The current study sought to determine the soil-modifying, crop yield improvement, and nematicidal properties of FA. In this study, beetroot seeds were sown in pots comprising field soil amended with differing proportions of FA (w/w) revealed the bio-fold properties of FA. Biomineralization and mapping of elements revealed that increased nutritional elements in soil supplemented with 15% FA induced growth-performance and yield of beetroot. Molecularly and morphologically characterized Meloidogyne incognita was used as nematode in this study for optimization of nematicidal properties FA. Plant growth performance, photosynthetic pigments, and yield of beetroot were significantly reduced owing to M. incognita as compared to control (un-treated and un-inoculated), and 15% FA reversed the negative effect of M. incognita significantly (P < 0.05) as compared to control plants. Confocal laser microscopy confirmed that 15% FA augmented in soil reduced nematode-juvenile invasion in beetroot as compared with control. The PCA (principal component analysis) accounted for 98.63% and 98.8% for the total-data variability in plants without nematodes and total data variability in treated plants (M. incognita + FA) respectively, which showed fit for a significant correlation between the various studied parameters in present study.

Design, Synthesis and Biological Assessment of Rhodanine-Linked Benzenesulfonamide Derivatives as Selective and Potent Human Carbonic Anhydrase Inhibitors.

A novel series of twenty-five rhodamine-linked benzenesulfonamide derivatives (7a-u and 9a-d) were synthesized and screened for their inhibitory action against four physiologically relevant human (h) carbonic anhydrase (CA) isoforms, namely hCA I, hCA II, hCA IX, and hCA XII. All the synthesized molecules showed good to excellent inhibition against all the tested isoforms in the nanomolar range due to the presence of the sulfonamide as a zinc binding group. The target compounds were developed from indol-3-ylchalcone-linked benzenesulfonamide where the indol-3-ylchalcone moiety was replaced with rhodanine-linked aldehydes or isatins to improve the inhibition. Interestingly, the molecules were slightly more selective towards hCA IX and XII compared to hCA I and II. The most potent and efficient ones against hCA I were 7h (KI 22.4 nM) and 9d (KI 35.8 nM) compared to the standard drug AAZ (KI 250.0 nM), whereas in case of hCA II inhibition, the derivatives containing the isatin nucleus as a tail were preferred. Collectively, all compounds were endowed with better inhibition against hCA IX compared to AAZ (KI 25.8 nM) as well as strong potency against hCA XII. Finally, these newly synthesized molecules could be taken as potential leads for the development of isoform selective hCA IX and XII inhibitors.

Comparison of effectiveness between Haloperidol and Quetiapine in acute manic episode.

This study was conducted to compare the response rate of Quetiapine and Haloperidol in patients with acute manic episodes. A total of 120 patients with acute episode of mania with baseline Young Mania Rating Scale (YMRS) of more than 20 were included and randomly allocated to either Quetiapine (Group A) or Haloperidol (Group B). Each patient was assessed at baseline. YMRS was administered at the start and at follow-up visit after six weeks. Comparison of response rate (>50% reduction in YMRS) was not statistically significant between the two groups (70% vs. 71.7%; p=0.410) after six weeks in acute manic episode. Quetiapine and Haloperidol emerged as equally effective pharmacological strategies for the treatment of bipolar mania. Quetiapine may be used as an alternative to conventional antipsychotics; Haloperidol can be used as replacement of Quetiapine as well, as it is of low cost.

An evolutionarily-conserved promoter allele governs HMG-CoA reductase expression in spontaneously hypertensive rat.

3-Hydroxy-3-methyl glutaryl-coenzyme A reductase (Hmgcr) encodes the rate-limiting enzyme in the cholesterol biosynthesis pathway. The regulation of Hmgcr in rat models of genetic hypertension (viz. Spontaneously Hypertensive Rat [SHR] and its normotensive control Wistar/Kyoto [WKY] strain) is unclear. Interestingly, Hmgcr transcript and protein levels are diminished in liver tissues of SHR as compared to WKY. This observation is consistent with the diminished plasma cholesterol level in SHR animals. However, the molecular basis of these apparently counter-intuitive findings remains completely unknown. Sequencing of the Hmgcr promoter in SHR and WKY strains reveals three variations: A-405G, C-62T and a 11 bp insertion (-398_-388insTGCGGTCCTCC) in SHR. Among these variations, A-405G occurs at an evolutionarily-conserved site among many mammals. Moreover, SHR-Hmgcr promoter displays lower activity than WKY-Hmgcr promoter in various cell lines. Transient transfections of Hmgcr-promoter mutants and in silico analysis suggest altered binding of Runx3 and Srebf1 across A-405G site. On the other hand, C-62T and -398_-388insTGCGGTCCTCC variations do not appear to contribute to the reduced Hmgcr promoter activity in SHR as compared to WKY. Indeed, chromatin immunoprecipitation assays confirm differential binding of Runx3 and Srebf1 to Hmgcr promoter leading to reduced expression of Hmgcr in SHR as compared to WKY under basal as well as cholesterol-modulated conditions. Taken together, this study provides, for the first time, molecular basis for diminished Hmgcr expression in SHR animals, which may account for the reduced circulating cholesterol level in this widely-studied model for cardiovascular diseases.

Biological control: a novel strategy for the control of the plant parasitic nematodes.

Plant parasitic nematodes (Root-knot nematodes, Meloidogyne spp.) are rounded worms, microscopic, and cause many agricultural economic losses. Their attacks have a direct impact on the productivity of cultivated crops by reducing their fruit quantity. Chemical control is widespread all over the world, but biological control is the most effective way to reduce the number of pests that infect crops, particularly by the use of microorganisms like fungi and bacteria. Biological control is rapidly evolving, and more products are being sold worldwide over time. They can be produced by fungi, bacteria, or actinomycetes that can destruct plant parasite nematodes and feed on them. Nematophagous microorganisms as the natural enemies of nematodes have a promising way of controlling nematodes. Some of them create net-like substances and traps to take the worms from outside and finally kill them. Other parasites serve as internal parasites in order to produce toxins and to produce virulence to kill nematodes. Comprehension of the molecular basis for microbial nematode interactions gives important insights into how successful biological nematode control agents can be created. We discuss recent advances in our understanding of nematodes and nematophagous microorganisms, with an emphasis on molecular mechanisms that infect nematodes with nematophagous microorganisms and on nematode safety from pathogenic attacks. Finally, we addressed numerous key areas for future research and development, including possible approaches to the application of our recent expertise in the development of successful biocontrol strategies.

Effects of Chronic Low-Dose Internal Radiation on Immune-Stimulatory Responses in Mice.

The Linear-No-Threshold (LNT) model predicts a dose-dependent linear increase in cancer risk. This has been supported by biological and epidemiological studies at high-dose exposures. However, at low-doses (LDR ≤ 0.1 Gy), the effects are more elusive and demonstrate a deviation from linearity. In this study, the effects of LDR on the development and progression of mammary cancer in FVB/N-Tg(MMTVneu)202Mul/J mice were investigated. Animals were chronically exposed to total doses of 10, 100, and 2000 mGy via tritiated drinking water, and were assessed at 3.5, 6, and 8 months of age. Results indicated an increased proportion of NK cells in various organs of LDR exposed mice. LDR significantly influenced NK and T cell function and activation, despite diminishing cell proliferation. Notably, the expression of NKG2D receptor on NK cells was dramatically reduced at 3.5 months but was upregulated at later time-points, while the expression of NKG2D ligand followed the opposite trend, with an increase at 3.5 months and a decrease thereafter. No noticeable impact was observed on mammary cancer development, as measured by tumor load. Our results demonstrated that LDR significantly influenced the proportion, proliferation, activation, and function of immune cells. Importantly, to the best of our knowledge, this is the first report demonstrating that LDR modulates the cross-talk between the NKG2D receptor and its ligands.

Influence of single-nucleotide polymorphisms in the IFNG towards susceptibility to tuberculosis in a Pakistani population.

Tuberculosis (TB) is a global issue as one-third of the population worldwide is considered to be infected. TB has become a critical public health problem as a result of increasing drug resistance, which poses a challenge to current control strategies. Similar to environmental factors, genetic makeup of the host equally contributes to disease onset. We performed genotypic analysis to examine the relationship between IFNG and TB onset and drug resistance in a Pakistani population comprising 689 subjects. Notable differences were observed in the IFNG polymorphism (+874T/A) between the case and control groups. The frequency of the wild-type genotype (TT) in the controls (43.2%) was significantly higher than in the cases (25.3%) (odds ratio [OR] = 0.77, p < 0.0001), while the mutant genotype frequency (AA) (38.57%) in the cases was significantly higher than in the controls (22.6%) (OR = 1.46, p < 0.0001). The heterozygous genotype frequency (TA) did not significantly differ between the control and case groups. Compared with the controls, the variant allele (A) was approximately twice as frequent in the cases. Females and older people have a higher chance of disease development. Finally, the IFNG (+874T/A) polymorphism was not associated with drug sensitivity or resistance. However, a genotypic polymorphism of IFNG (+874T/A) was significantly associated with susceptibility to TB, and the T allele conferred protection against TB. Additional studies involving larger cohorts are needed to further explore this relationship between genetics and disease vulnerability.

A haplotype variant of the human chromogranin A gene (CHGA) promoter increases CHGA expression and the risk for cardiometabolic disorders.

The acidic glycoprotein chromogranin A (CHGA) is co-stored/co-secreted with catecholamines and crucial for secretory vesicle biogenesis in neuronal/neuroendocrine cells. CHGA is dysregulated in several cardiovascular diseases, but the underlying mechanisms are not well established. Here, we sought to identify common polymorphisms in the CHGA promoter and to explore the mechanistic basis of their plausible contribution to regulating CHGA protein levels in circulation. Resequencing of the CHGA promoter in an Indian population (n = 769) yielded nine single-nucleotide polymorphisms (SNPs): G-1106A, A-1018T, T-1014C, T-988G, G-513A, G-462A, T-415C, C-89A, and C-57T. Linkage disequilibrium (LD) analysis indicated strong LD among SNPs at the -1014, -988, -462, and -89 bp positions and between the -1018 and -57 bp positions. Haplotype analysis predicted five major promoter haplotypes that displayed differential promoter activities in neuronal cells; specifically, haplotype 2 (containing variant T alleles at -1018 and -57 bp) exhibited the highest promoter activity. Systematic computational and experimental analyses revealed that transcription factor c-Rel has a role in activating the CHGA promoter haplotype 2 under basal and pathophysiological conditions (viz. inflammation and hypoxia). Consistent with the higher in vitro CHGA promoter activity of haplotype 2, individuals carrying this haplotype had higher plasma CHGA levels, plasma glucose levels, diastolic blood pressure, and body mass index. In conclusion, these results suggest a functional role of the CHGA promoter haplotype 2 (occurring in a large proportion of the world population) in enhancing CHGA expression in haplotype 2 carriers who may be at higher risk for cardiovascular/metabolic disorders.

Functional promoter polymorphisms direct the expression of cystathionine gamma-lyase gene in mouse models of essential hypertension.

Despite the well-known role of cystathionine γ-lyase (Cth) in cardiovascular pathophysiology, transcriptional regulation of Cth remains incompletely understood. Sequencing of the Cth promoter region in mouse models of genetic/essential hypertension (viz. Blood Pressure High [BPH], Blood Pressure Low [BPL] and Blood Pressure Normal [BPN] mice) identified several genetic variations. Transient transfections of BPH/BPL-Cth promoter-reporter plasmids into various cell types revealed higher promoter activity of BPL-Cth than that of BPH-Cth. Corroboratively, endogenous Cth mRNA levels in kidney and liver tissues were also elevated in BPL mice. Computational analysis of the polymorphic Cth promoter region predicted differential binding affinity of c-Rel, HOXA3 and IRF1 with BPL/BPH-Cth promoter domains. Over-expression of c-Rel/HOXA3/IRF1 modulated BPL/BPH-Cth promoter activities in a consistent manner. Gel shift assays using BPH/BPL-Cth-promoter oligonucleotides with/without binding sites for c-Rel/HOXA3/IRF1 displayed formation of specific complexes with c-Rel/HOXA3/IRF1; addition of antibodies to reaction mixtures resulted in supershifts/inhibition of Cth promoter-transcription factor complexes. Furthermore, chromatin immunoprecipitation (ChIP) assays proved differential binding of c-Rel, HOXA3 and IRF1 with the polymorphic promoter region of BPL/BPH-Cth. Tumor necrosis factor-α (TNF-α) reduced the activities of BPL/BPH-Cth promoters to different extents that were further declined by ectopic expression of IRF1; on the other hand, siRNA-mediated down-regulation of IRF1 rescued the TNF-α-mediated suppression of the BPL/BPH-Cth promoter activities. In corroboration, ChIP analysis revealed enhanced binding of IRF1 with BPH/BPL-Cth promoter following TNF-α treatment. BPL/BPH-Cth promoter activity was diminished upon exposure of hepatocytes and cardiomyoblasts to ischemia-like pathological condition due to reduced binding of c-Rel with BPL/BPH-Cth-promoter. Taken together, this study reveals the molecular basis for the differential expression of Cth in mouse models of essential hypertension under basal and pathophysiological conditions.

Advances in treatment of metastatic renal cell carcinoma.

PURPOSE OF REVIEW: Multiple agents, including vascular endothelial growth factor (VEGF) inhibitors and mammalian target of rapamycin inhibitors have been approved over the past decade for the treatment of metastatic renal cell carcinoma (mRCC). Here, we focus on nivolumab, cabozantinib, and lenvatinib plus everolimus, agents that have recently emerged with positive clinical data leading to 'Food and Drug Administration approval or pending approval in mRCC. We also review the development of novel agents of interest showing promise in mRCC as part of combination therapy'. RECENT FINDINGS: Nivolumab and cabozantinib both offer improved survival over everolimus in the second-line treatment of mRCC. Lenvatinib plus everolimus has similarly shown encouraging survival benefits in a phase II trial for the second-line setting. Novel combinations in mRCC, including dual immune checkpoint blockade, VEGF and programmed death 1 inhibition, VEGF and vaccine therapy, dual angiogenic blockade, and VEGF-directed therapy with nanoparticle-containing camptothecin have shown promising activity in early-phase trials. SUMMARY: Multiple promising agents are available in the treatment of mRCC. The appropriate sequencing of agents in the treatment of mRCC may become further elucidated by future studies that prospectively analyze potential biomarkers to identify patients who will derive the greatest benefit from VEGF, mammalian target of rapamycin, or checkpoint inhibitors.

Molecular mechanism of monoamine oxidase A gene regulation under inflammation and ischemia-like conditions: key roles of the transcription factors GATA2, Sp1 and TBP.

Monoamine oxidase A (MAOA) plays important roles in the pathogenesis of several neurological and cardiovascular disorders. The mechanism of transcriptional regulation of MAOA under basal and pathological conditions, however, remains incompletely understood. Here, we report systematic identification and characterization of cis elements and transcription factors that govern the expression of MAOA gene. Extensive computational analysis of MAOA promoter, followed by 5'-promoter deletion/reporter assays, revealed that the -71/-40 bp domain was sufficient for its basal transcription. Gel-shift and chromatin immunoprecipitation assays provided evidence of interactions of the transcription factors GATA-binding protein 2 (GATA2), Sp1 and TATA-binding protein (TBP) with this proximal promoter region. Consistently, over-expression of GATA2, Sp1 and TBP augmented MAOA promoter activity in a coordinated manner. In corroboration, siRNA-mediated down-regulation of GATA2/Sp1/TBP repressed the endogenous MAOA expression as well as transfected MAOA promoter activity. Tumor necrosis factor-α and forskolin activated MAOA transcription that was reversed by Sp1 siRNA; in support, tumor necrosis factor-α- and forskolin-induced activities were enhanced by ectopic over-expression of Sp1. On the other hand, MAOA transcription was diminished upon exposure of neuroblasts or cardiac myoblasts to ischemia-like conditions because of reduced binding of GATA2/Sp1/TBP with MAOA promoter. In conclusion, this study revealed previously unknown roles of GATA2, Sp1 and TBP in modulating MAOA expression under basal as well as pathophysiological conditions such as inflammation and ischemia, thus providing new insights into the molecular basis of aberrant MAOA expression in neuronal/cardiovascular disease states. Dysregulation of monoamine oxidase A (MAOA) have been implicated in several behavioral and neuronal disease states. Here, we identified three crucial transcription factors (GATA2, Sp1 and TBP) that regulate MAOA gene expression in a coordinated manner. Aberrant MAOA expression under pathophysiological conditions including inflammation and ischemia is mediated by altered binding of GATA2/Sp1/TBP with MAOA proximal promoter. Thus, these findings provide new insights into pathogenesis of several common diseases. GATA2, GATA-binding protein 2; Sp1, specificity protein 1; TBP, TATA-binding protein.

Transcriptional regulation of the novel monoamine oxidase renalase: Crucial roles of transcription factors Sp1, STAT3, and ZBP89.

Renalase, a novel monoamine oxidase, is emerging as an important regulator of cardiovascular, metabolic, and renal diseases. However, the mechanism of transcriptional regulation of this enzyme remains largely unknown. We undertook a systematic analysis of the renalase gene to identify regulatory promoter elements and transcription factors. Computational analysis coupled with transfection of human renalase promoter/luciferase reporter plasmids (5'-promoter-deletion constructs) into various cell types (HEK-293, IMR32, and HepG2) identified two crucial promoter domains at base pairs -485 to -399 and -252 to -150. Electrophoretic mobility shift assays using renalase promoter oligonucleotides with and without potential binding sites for transcription factors Sp1, STAT3, and ZBP89 displayed formation of specific complexes with HEK-293 nuclear proteins. Consistently, overexpression of Sp1, STAT3, and ZBP89 augmented renalase promoter activity; additionally, siRNA-mediated downregulation of Sp1, STAT3, and ZBP89 reduced the level of endogenous renalase transcription as well as the transfected renalase promoter activity. In addition, chromatin immunoprecipitation assays showed in vivo interactions of these transcription factors with renalase promoter. Interestingly, renalase promoter activity was augmented by nicotine and catecholamines; while Sp1 and STAT3 synergistically activated the nicotine-induced effect, Sp1 appeared to enhance epinephrine-evoked renalase transcription. Moreover, renalase transcript levels in mouse models of human essential hypertension were concomitantly associated with endogenous STAT3 and ZBP89 levels, suggesting crucial roles for these transcription factors in regulating renalase gene expression in cardiovascular pathological conditions.

Role of Toll-like receptor 2 (-196 to -174) polymorphism in susceptibility to pulmonary tuberculosis in Pakistani population.

Tuberculosis (TB) is a global public health problem and a source of preventable deaths each year, with 8.8 million new cases of TB and 1.6 million deaths worldwide. Pakistan ranks sixth on the list of 22 high-burden tuberculosis countries in the world. The transitions from infection to clinical disease are very few signifying that host-defence factors could lead to the development of active disease. Toll-like receptor (TLR) 2 polymorphisms have been associated with regulation of TLR expression and development of active TB. In this study, blood samples of 187 subjects including 100 healthy and 87 TB positive were collected from three districts of Pakistan. DNA was extracted from blood and TLR 2 (-196 to -174del) polymorphism was analysed by polymerase chain reaction (PCR). The results suggest that the frequency of -196 to -174del/del polymorphism of TLR2 was significantly higher in TB-positive patients compared with healthy. Results revealed that (-196 to -174del) polymorphism may increase the susceptibility to TB in healthy population of Pakistan. Moreover, males with heterozygous genotype (I/D) are more prone to TB than females with the same genotype. The occurrence of TB infection has been found positively associated with the age, suggesting that the population within the range of 21-45 years is more susceptible to Mycobacterium tuberculosis than other age groups studied. A significant association is also observed between smoking and the chances of developing TB, confirming that smoking strongly promotes its incidence.

Endophytic fungi: Unravelling plant-endophyte interaction and the multifaceted role of fungal endophytes in stress amelioration.

Endophytic fungi colonize interior plant tissue and mostly form mutualistic associations with their host plant. Plant-endophyte interaction is a complex mechanism and is currently a focus of research to understand the underlying mechanism of endophyte asymptomatic colonization, the process of evading plant immune response, modulation of gene expression, and establishment of a balanced mutualistic relationship. Fungal endophytes rely on plant hosts for nutrients, shelter, and transmission and improve the host plant's tolerance against biotic stresses, including -herbivores, nematodes, bacterial, fungal, viral, nematode, and other phytopathogens. Endophytic fungi have been reported to improve plant health by reducing and eradicating the harmful effect of phytopathogens through competition for space or nutrients, mycoparasitism, and through direct or indirect defense systems by producing secondary metabolites as well as by induced systemic resistance (ISR). Additionally, for efficient crop improvement, practicing them would be a fruitful step for a sustainable approach. This review article summarizes the current research progress in plant-endophyte interaction and the fungal endophyte mechanism to overcome host defense responses, their subsequent colonization, and the establishment of a balanced mutualistic interaction with host plants. This review also highlighted the potential of fungal endophytes in the amelioration of biotic stress. We have also discussed the relevance of various bioactive compounds possessing antimicrobial potential against a variety of agricultural pathogens. Furthermore, endophyte-mediated ISR is also emphasized.

Exploiting fly ash as an ecofriendly pesticide/nematicide on Abesmoschus esculuntus: Insights into soil amendment-induced antioxidant fight against nematode mediated ROS.

Conventional pest control measures, such as chemical pesticides and nematicides, have limited efficacy and raise environmental concerns, necessitating sustainable and eco-friendly alternatives for pest management. Therefore, to find a complementary eco-friendly pesticide/nematicide, this study investigated the role of fly ash (FA) in managing a notorious pest, Meloidogyne javanica and its impact on the growth and physiology of Abelmoschus esculentus. Molecular characterization using SSU and LSU rDNA gene markers confirmed the identity of Indian M. javanica as belonging to the same species. Biotic stress induced by nematode infection was significantly alleviated (P < 0.05) by FA application at a 20% w/v, regulating of ROS accumulation (44.1% reduction in superoxide anions and 39.7% reduction in hydrogen peroxide content) in the host plant. Moreover, FA enhanced antioxidant defence enzymes like superoxide dismutase (46.6%) and catalase (112%) to combat nematode induced ROS. Furthermore, the application of FA at a 20% concentration significantly improved the biomass and biochemical attributes of okra. Fly ash also upregulated the activity of the important osmo-protectant proline (11.5 µmol/g FW) to mitigate nematode stress in host cells. Suppression of disease indices like gall index and reproduction factor, combined with in-vitro experiments, revealed that FA exhibits strong nematode mortality capacity and thus can be used as a sustainable and eco-friendly control agent against root-knot nematodes.

Development of a recycling machine for constructing synthetic yarn from plastic waste.

A major challenge in plastic recycling is to convert plastic waste into a useful product. For this transformation, sustainable technologies such as plastic recycling machines are required. Current technological concepts of plastic recycling are fairly similar. This study aims to develop a small and economical plastic recycling machine to enhance microenterprise by supplying simple equipment for recycling locally processed plastic waste into thread. Starting with a hopper at the input end, the machine incorporates an auger inside a barrel, which is then linked to a metallic perforated mold at the output end. With the help of the system, the plastic flakes melting process is facilitated by maintaining temperatures between 170 °C to 211 °C at equispaced locations of a uniform barrel, while the auger spin enables the flow of molten plastic forward towards the mold.The mold reshapes the liquid plastic into strings of thread. The machine exhibits higher efficiency, reaching approximately 75 % at a decreased screw speed, as low as 28 rpm. It also achieves an average throughput of 156 gm/hour at the lowest specific mechanical energy (SME) consumption. The prototype consumes 1.5 kW for an hour operation. The entire system requires minimal space, making it appealing to individuals with limited financial resources to start a new business venture.•A sustainable technology to recycle plastic waste into plastic thread.•This optimized, portable and robust system ensures safety and lower operating costs.•This system does not require prior knowledge for operation, hence encouraging small entrepreneurs.